Nautilus Biotech And Creabilis Therapeutics Achieve Technical Milestone In Collaboration To Improve HMGB1 Box A For The Treatment Of Rage- And HMGB1-Related Pathologies 11/14/2006 10:41:43 AM

PARIS, France, and COLLERETTO GIACOSA, Italy, November 14 /PRNewswire/ -- Nautilus Biotech SA and Creabilis Therapeutics SpA have announced that they have shown increased biological activity and resistance to proteolysis in vitro of the High Mobility Group Box One (HMGB1) Box A protein, an important technical milestone in their collaboration to identify a potential candidate drug for the treatment of RAGE- (Receptor for Advanced Glycation End products) and HMGB1-related pathologies, which include hepatitis B, rheumatoid arthritis, melanoma and sepsis.

HMGB1 is an abundant nuclear and cytoplasmic protein present in mammalian cells, which, when released, is known to play an important role in the pathogenesis of several diseases. Native HMGB1 Box A (a DNA-binding domain of HMGB1) is a specific antagonist of whole HMGB1 on the RAGE receptor. Highly purified native Box A has been shown to successfully protect against sepsis and other RAGE and HMGB1-related diseases in animal models.

Nautilus Biotech and Creabilis Therapeutics entered into collaboration in September 2004 with the aim to develop a drugable variant of native HMBG1 Box A with improved PK/PD characteristics to be used as a direct antagonist of HMGB1 to treat related pathologies including hepatitis B, rheumatoid arthritis, SLE, melanoma, sepsis and MS and/or as inhibitor of RAGE to treat diabetes complications and inflammatory diseases. Using its proprietary protein engineering technology, Nautilus Biotech created a series of single amino acid variants of the native Box A protein. Creabilis has now completed testing of all the variants and has shown that a limited number of these have increased biological activity in vitro and greater resistance to proteolysis. Creabilis is now testing these improved molecules in vivo and plans to select the lead molecule for preclinical development in Q1 2007.

Commenting on the announcement, Dr Manuel Vega, CEO Nautilus Biotech said: "I am delighted to announce the achievement of this important milestone in our collaboration with Creabilis Therapeutics, which represents further external validation of Nautilus core technology for protein engineering. Increasing resistance to proteolysis and improving biological activity offers important improvements in drug profiles and has the potential to create highly differentiated therapeutic products with better patient compliance. Nautilus Biotech's technology has wide applicability across many therapeutic protein families and this collaboration has demonstrated the success of our technology when applied to small proteins such as HMGB1 Box A, opening the way to other small proteins and peptides of big clinical potential and market value."

Dr. Silvano Fumero, CEO Creabilis Therapeutics, said: "We are very pleased with the results so far achieved in this project as they are a confirmation of the potential of Nautilus' proprietary technology when applied to early development stage proteins. Native Box A has been demonstrated to be active in experimental models but with a very poor PK profile. Some of the variants obtained with Nautilus' technology are now potential drugable compounds.

Nautilus Biotech has already used its technology to develop injectable BELEROFON(R), its protease-resistant, long-lasting Interferon (IFN) alpha, which has therapeutic potential for the treatment of a number of clinical diseases, including Chronic Hepatitis C. Nautilus expects to commence a Phase 1 study in the US in Q1 2007, with the aim of confirming the enhanced pharmacological profile of subcutaneous BELEROFON(R).

Notes to Editors:

About Nautilus Biotech

Nautilus Biotech is a drug discovery company with a pipeline of next-generation therapeutic proteins with superior pharmacological profiles that address unmet clinical needs. The Company's protein engineering technology can significantly improve the pharmacological characteristics of important blockbuster protein drugs, offering improvements in drug stability and administration. The Company is also creating proprietary 'third generation' therapeutic proteins which are, per se, suitable for oral administration.

The therapeutic proteins market is currently valued at over $30bn, and growing at a rate of 10-15% per annum. Nautilus has created a portfolio of next-generation therapeutic proteins with improved profiles, including long lasting Interferon alpha (Belerofon(R)), hGH (Vitatropin(tm)), Interferon beta, Clotting Factor IX, Erythropoietin, Interferon gamma and HMG-B1; it has established a strong intellectual property position covering enhanced versions of these multibillion dollars molecules and is rapidly moving these products towards clinical phases.

Nautilus Biotech is a private company with headquarters in Genopole(R) biopark, (Evry, France). For more information about Nautilus Biotech visit www.nautilusbiotech.com

About Creabilis Therapeutics

CREABILIS Therapeutics is a drug discovery and development biotech company, founded in May 2003 with the aim to discover, select, develop and bring to commercial fruition novel and highly innovative therapeutic agents. After three years of research activity a considerable, competitive and diversified project/product portfolio has been generated. CREABILIS is today strongly committed to exploit the potential of its discovery assets and to develop its novel proprietary candidate products. In addition to HMGB1 Box A, CREABILIS is developing also direct inhibitors of HMGB1. The most advanced project is related to CT327 in the topical treatment of psoriasis: a Phase I clinical trial is planned in 2Q 2007. For more information about Creabilis Therapeutics visit http://www.creabilistherapeutics.com/